MTRFR

mitochondrial translation release factor in rescue, the group of Mitochondrial translation release factor family

Basic information

Region (hg38): 12:123233385-123258079

Previous symbols: [ "C12orf65" ]

Links

ENSG00000130921

∙ NCBI:91574 ∙ OMIM:613541 ∙ HGNC:26784 ∙ Uniprot:Q9H3J6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

combined oxidative phosphorylation defect type 7 (Definitive), mode of inheritance: AR
Leigh syndrome (Definitive), mode of inheritance: AR
combined oxidative phosphorylation defect type 7 (Moderate), mode of inheritance: AR
combined oxidative phosphorylation defect type 7 (Strong), mode of inheritance: AR
Leigh syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 7; Spastic paraplegia 55, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic; Ophthalmologic	3479531; 20598281; 23188110; 24198383

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MTRFR gene.

Combined oxidative phosphorylation defect type 7;Spastic paraplegia (6 variants)
Hereditary spastic paraplegia 55 (3 variants)
not provided (3 variants)
Neurodevelopmental disorder (1 variants)
Combined oxidative phosphorylation defect type 7;Hereditary spastic paraplegia 55 (1 variants)
Spastic paraplegia;Combined oxidative phosphorylation defect type 7 (1 variants)
Combined oxidative phosphorylation defect type 7 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MTRFR gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				25 clinvar	1 clinvar	26
missense		1 clinvar	54 clinvar		1 clinvar	56
nonsense	2 clinvar	2 clinvar				4
start loss						0
frameshift	8 clinvar	5 clinvar	1 clinvar			14
inframe indel			3 clinvar			3
splice donor/acceptor (+/-2bp)		1 clinvar				1
splice region				2		2
non coding			21 clinvar	14 clinvar	7 clinvar	42
Total	10	9	79	39	9

Highest pathogenic variant AF is 0.0000657

Variants in MTRFR

This is a list of pathogenic ClinVar variants found in the MTRFR region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Phenotype	Significance	ClinVar
12-123233394-T-C	Combined oxidative phosphorylation defect type 7	Uncertain significance (Jan 13, 2018)	882665
12-123233428-A-G	Combined oxidative phosphorylation defect type 7	Uncertain significance (Jan 12, 2018)	882666
12-123233432-C-T	Combined oxidative phosphorylation defect type 7	Uncertain significance (Jan 13, 2018)	307493
12-123233509-C-T	Combined oxidative phosphorylation defect type 7	Uncertain significance (Jan 12, 2018)	882667
12-123233754-C-T		Benign (Jun 18, 2018)	671535
12-123252157-GATGCAGTGGCTCACGCCTGTAATCCCAGAACTTTGGGAGGCTGAAGCAGGTGGATTACTTGACCTTAGGGAGTTCAAGACCAGCCTGGGCAATATGGCGAAACCCCATCTCTACAAAAAGTAATTACTCAGATGTGGTGGTGTCTGCCTGTAGTCTTCACCTACTAGGGAGCCTGAGGTGACAGAATCGCCTGACCCTGGGGAAGTCAAGGCTGCAGTGAGCTGTGATCGCGCCACTGCAGTCCAGCCTGGGCGACAGAGTGGGACTCTGTCTCAAAAAAAAAAAAAAAATTAGTTGACTTGGTAGTTCCAACGATGAGTACCAGTTGGACCACGTTGTTGGCAGTGCGTCCAGGGAACAGATGTTCACATTCAAATCCATGAAACTGGAAACAAAAAACAACAATCATGACATTGATTGATAGTGATGTTTACTATGTCAGACTGTTTAAGCTCAGCTATAAAATAGACTACTCAGCCCTGGGTGGGGGTGGGGGGTGGCTCACACTTGTAATCCCAGCACTTTGGGAGGCCGAGGTGGGCAGATCACCTGAGGTCAGGAATTCGAGACCAGCCTGGCCAACATGGTGAATCCCCGCCTCTACTAAAAATACAAAAATTAGCCGGGTGTGGTGGCACACGCCTGTAATCCCAGCTACTCAGGAGGCTGAGGCAGGAGAATCACTTGAACCTGGGAGGCGGAGGTTGCAGTGAGCCAAGATCGCGCCATCGCACTCCAGCCTGGGCGACAGAGCGAGATTCCGTCTCAAAAAATAAAATAGACTCTCATACTGTCATCTTTACATTTTGATTTCAGAGATTCTCAAACATTTAAATACTGGCACTTGACCCAGATCCTAATTTTTGCTTGATGCACTATTTACCTGTATCAAATTACAGTCCGTTCCTTTGAATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTGAGACACTGTCTCGCTCTGTTGTCCAGGCTGGAGTGCAGTGGCTCTGCCTCAGCCTCCCGAGTAGCTGGGATTACAGGCACCCACCACCAAGCCCGGCTAATTTTTGTATTTTTAGTAGAGATAGTTTCATCATCTTGGCCAGGCTGGTCTTGAACTCCTGACCTTGTGATCCACCTGCCTCGGCCTCCCAAAGTGCTTGGATTACAGGTGTGAGCCACCATGCCCGGCCTGAATTTCACACTCAAAACCTCTCCTTTCTGAGAAAACAGCACCCCCGGGTGCTTGGAAGATATTTTTGGTCTATTGCAAGAAAATATGTATTAGCTGGCAGGGCATGTCCTGGTAACATGGCAGACAGTGCAAGGCTGAGGAGAGGGGCGTCTTGCTGAATAATGTGTCTCTACTCATTTCCTAAATTCCCTCGGTAACAGATGGGTCATCATTTGAATTGCTTTATAAAAAGCTGTCTTTGAATCTGAAGCATAATCTTGAGGGCAGATGCCTCTTACTGAAAGCTCTCCTTATTCATCTAACCCAGGTCCTCAGCCAGCAGAGCCACGTTCCTTATGAGCACCGTGGGTTTATTTCATTTTCCTACACCACTGACCCGAATATGCCCGGCGCCATGGGGACTCCGGCTTTGGGAGAAGCTGACGTTGTTATCCCCAGGAATAGCTGTCACTCCGGTCCAGATGGCAGGCAAGAAGGACTACCCTGCACTGCTTTCCTTGGATGAGAATGAACTCGAAGAGCAGTTTGTGAAAGGACACGGTCCAGGGGGCCAGGCAACCAACAAAACCAGCAACTGCGTGGTGCTGAAGCACATCCCCTCAGGCATCGTTGTAAAGGTAGATCACAGAAGGCCGCTGAGGGGAGAGGCCCCGCCCAAGGGTTCCACAGCCTCCAGAGATTTCTCCCAAGTGTGAATGGGATCAGCCGAAGTGCATTATTTTTCTGGCTTGGGCCACCCTCTACCAGCCAGGCAGTAGAGAGCACCGCAGATCTCGTCCCATCCCTGAGCCATTCCTCCCTAAGGCAGAACCTCCTACAACAGCCTGGGAAGCCTGTTTCCAGGATCTTTTGGAGCCAGGGTATGGCTGCCATCCTTGAATTTGGCAGACAGCACTGGTGCTTGGCTGCTGCCCCGGAAGCAACGTCTTGACAAAGCTAAGCAGTGGCTGATAAAGGCAGGCGCCCGGGCAGCATGGTTCTTTCAAATCCGTTCCCACTGCAGGAAGGCTGCCGAGATCCCCAGCATTGCTATGGGATCCAAGTCCCTGAGGAGGCGGCAAGCAGGCATGGGTTGTCTGCTGGCAGTCCCAGCCCTTAACTGTCATGGCTGGTTAACATTAGGGTGGCCACATCCTCCACGCCTCTCTGTCCCCTTTGGTAAATGTCGGTGATACCTCCTCTTCTGGACAGAGAGGACTGAGGGCGAGATCATGGAGGATCATGGAGGCCAGGCATTTTCCAACCTCAGAAGAAAAAATGCTGTGCACAGCTGCCTATAGGAGTCTTCCTTTTTACATAAAAAAACAAGTCTCGGGCCAGGCACAGTGGCTCATGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGTGGGTGGATCACCTGAGGTCAGGAGTTCGAGACCAGTCTGGTCAACATGGCAAAACCCCATCTCTACTGAAAATACAAAAATTAGCCGGGTGTGGTGGCGCGTGCCTGTAATCCCAGTTACTCGGAGGCTAAGGCAGGAGAATCGCTTGAACCCTGGAGGCAGACATTGCAGTGAGCCGAGATCATGCTACTGCATACCAGCCTGGGCAACAGACAAGATTCCCTCTTAAAAAAAAAAAAAAGAAGGTTGGTCAGAGGGGCTCCCAGTCCATCTGCCTCAGGGATCACGAGAGAGTCCTGGAAGCAGCACAGAAGAGAGATAGCCAAGGCAGGTGTTTCATATATAACGATACTGGCAGCAGATACTTACAGGTCATGGAAACGTGTGGGAGGAACTGTTCGAAGCAGCATTAACTCTGCAGTCCCCAAAACCCCATGTTCATGATTTCCATCACAGTACAGGTGTGGAATCTGGGACATAGAGAGGCTAAGTGACCTGCCCAAGGTCCTGCCACTCAGTAGTCAGTTCACACCATACCCCAAGTCCATGTTCCTAACAGCTGCACTTCACTGCTGGGTTTCTGAGCCACAAGCATATCATGTAAAACCTCAATCATTTCTTTTCCCCCTTGAAAAGTGTCATTCATGAGTAACAAAATTCTGAAACCTGAGAGTTAATTTTTGTTTAACCTATTTGACATAACTCAATCCAAACTTGCTTTCAGAATTATTCTTTAACCCTAATTTCATAGAATTTTTTTTTTTTTAAGAGACAGGGTCTTGTTTTGTCAGCCAGGTTGGAGTGCAGTGGTGCAATCATGGCTCAGTATAGCCTCAAACACCTGGGCTCAAGCAATCCTCCCGCCTCGGCCTCCCGAGTAGCTGGGACTGCAGGCATGCCCCACCACACTCAGTGTTTTTTGTTTCGTTTTGTTTTTTGAGACAGTCTTGCTCTATTGCCCAGGCTGGAGTGCAGTGGCGCAATCTCAGCTCACTGCAACGTCCGCCTCCTGGGTTCAAGCAATTCTCCTGCCTCAGCCTCCCGAGTAGCTGGGATTACAGGTGCCCATCACCACGCCCAGCTAATTTTTTTGTATTTTTACTAGAGACAAGGTTTCACCATGTTGGCCAGGCTGGTTT-G	Neurodevelopmental disorder	Pathogenic (Apr 09, 2019)	635867
12-123253386-G-T		Benign (Jun 14, 2018)	680559
12-123253667-C-T	MTRFR-related disorder	Likely benign (May 28, 2019)	3038885
12-123253683-C-T	Combined oxidative phosphorylation defect type 7;Spastic paraplegia	Likely benign (Mar 09, 2022)	2419174
12-123253688-GTTTA-G	Hereditary motor and sensory neuropathy with optic atrophy	Likely pathogenic (Dec 01, 2020)	1048600
12-123253696-C-G	Spastic paraplegia;Combined oxidative phosphorylation defect type 7	Uncertain significance (Aug 10, 2022)	1929241
12-123253700-T-C	Spastic paraplegia;Combined oxidative phosphorylation defect type 7	Uncertain significance (Apr 27, 2023)	2067895
12-123253706-C-T	Combined oxidative phosphorylation defect type 7;Spastic paraplegia	Uncertain significance (Aug 16, 2021)	1681651
12-123253706-C-CA	Spastic paraplegia;Combined oxidative phosphorylation defect type 7	Pathogenic (Feb 05, 2019)	859045
12-123253708-C-T	Combined oxidative phosphorylation defect type 7 • Combined oxidative phosphorylation defect type 7;Spastic paraplegia	Uncertain significance (Jan 09, 2023)	307494
12-123253715-C-T	Combined oxidative phosphorylation defect type 7;Spastic paraplegia	Uncertain significance (Aug 04, 2023)	2037642
12-123253717-C-T		Likely pathogenic (Dec 18, 2022)	1323989
12-123253718-G-A	not specified • Combined oxidative phosphorylation defect type 7;Spastic paraplegia • Hereditary spastic paraplegia • Combined oxidative phosphorylation defect type 7	Benign (Jan 31, 2024)	128535
12-123253721-T-C		Uncertain significance (Jul 28, 2022)	2412984
12-123253727-C-T	Combined oxidative phosphorylation defect type 7;Spastic paraplegia	Uncertain significance (May 06, 2022)	502352
12-123253728-G-A	Combined oxidative phosphorylation defect type 7;Spastic paraplegia • Hereditary spastic paraplegia	Conflicting classifications of pathogenicity (Jan 17, 2024)	697230
12-123253730-C-T	Combined oxidative phosphorylation defect type 7 • Combined oxidative phosphorylation defect type 7;Spastic paraplegia	Uncertain significance (Aug 19, 2022)	307495
12-123253731-G-A	Combined oxidative phosphorylation defect type 7;Spastic paraplegia	Likely benign (Nov 27, 2018)	700950
12-123253745-G-A	Spastic paraplegia;Combined oxidative phosphorylation defect type 7	Uncertain significance (Feb 27, 2024)	1212115
12-123253745-G-T	Spastic paraplegia;Combined oxidative phosphorylation defect type 7	Uncertain significance (Mar 11, 2022)	1309118

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MTRFR	protein_coding	protein_coding	ENST00000253233	2	25044

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.209	0.754	125657	0	91	125748	0.000362

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.433	102	90.4	1.13	0.00000531	1063
Missense in Polyphen		28	30.652	0.91349		355
Synonymous	1.13	30	38.9	0.770	0.00000256	330
Loss of Function	1.74	2	6.94	0.288	4.80e-7	69

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000616	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00111	0.00111
European (Non-Finnish)	0.000537	0.000536
Middle Eastern	0.000109	0.000109
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: May act as a codon-independent translation release factor that has lost all stop codon specificity and directs the termination of translation in mitochondrion. May help rescuing stalled mitoribosomes during translation (By similarity). {ECO:0000250}.;
Disease: DISEASE: Combined oxidative phosphorylation deficiency 7 (COXPD7) [MIM:613559]: A mitochondrial disease resulting in encephalomyopathy. Clinical manifestations include psychomotor delay and regression, ataxia, optic atrophy, nystagmus and muscle atrophy and weakness. {ECO:0000269|PubMed:20598281}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spastic paraplegia 55, autosomal recessive (SPG55) [MIM:615035]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. Complicated forms are recognized by additional variable features including spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra neurological manifestations. {ECO:0000269|PubMed:23188110}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0748

Intolerance Scores

loftool: 0.863
rvis_EVS: 0.13
rvis_percentile_EVS: 63

Haploinsufficiency Scores

pHI: 0.0565
hipred: N
hipred_score: 0.267
ghis: 0.510

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: E
essential_gene_gene_trap: H
gene_indispensability_pred
gene_indispensability_score

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: 2810006K23Rik
Phenotype

Gene ontology

Biological process: translational termination
Cellular component: mitochondrion;mitochondrial large ribosomal subunit
Molecular function: translation release factor activity